[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing’s syndrome

in European Journal of Endocrinology
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  • 1 Departments of Endocrinology and 1Nuclear Medicine, Middlesex Hospital, Mortimer Street, London W1T 3AA, UK

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We report a case of a young woman with Cushing’s syndrome (CS), in whom although endocrine investigations and negative pituitary imaging were suggestive of ectopic ACTH secretion, the results of inferior petrosal sinus (IPS) sampling after coricotropin-releasing hormone (CRH) stimulation were suggestive of pituitary ACTH hypersecretion. 111In-labelled octreotide and high-resolution computer tomography (CT) revealed a lesion possibly responsible for the ACTH source in the thymus. Thymectomy confirmed concomitant ectopic CRH and probable ACTH production by a thymic neuroendocrine carcinoma. After an 8-year remission period the patient developed a clinical and biochemical relapse. A high-resolution computed tomography (CT) scan of the thorax showed a 2-cm nodule in the thymic bed, which was positive on a [18F]fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography (PET) scan. However, a repeated thymectomy did not result in remission. A repeat [18F]FDG PET study showed persistent disease in the thymic bed and also uptake in the adrenals. The patient underwent bilateral adrenalectomy, which resulted in clinical remission. A further [18F]FDG PET scan 8 months later showed no progression of the thymic tumor and confirmed complete excision of the adrenals. This is a rare case of concomitant CRH and ACTH secretion from a thymic carcinoid tumor; the case illustrates the usefulness of functional imaging with [18F]FDG PET in the diagnosis, management and follow-up of neuroendocrine tumors.

Abstract

We report a case of a young woman with Cushing’s syndrome (CS), in whom although endocrine investigations and negative pituitary imaging were suggestive of ectopic ACTH secretion, the results of inferior petrosal sinus (IPS) sampling after coricotropin-releasing hormone (CRH) stimulation were suggestive of pituitary ACTH hypersecretion. 111In-labelled octreotide and high-resolution computer tomography (CT) revealed a lesion possibly responsible for the ACTH source in the thymus. Thymectomy confirmed concomitant ectopic CRH and probable ACTH production by a thymic neuroendocrine carcinoma. After an 8-year remission period the patient developed a clinical and biochemical relapse. A high-resolution computed tomography (CT) scan of the thorax showed a 2-cm nodule in the thymic bed, which was positive on a [18F]fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography (PET) scan. However, a repeated thymectomy did not result in remission. A repeat [18F]FDG PET study showed persistent disease in the thymic bed and also uptake in the adrenals. The patient underwent bilateral adrenalectomy, which resulted in clinical remission. A further [18F]FDG PET scan 8 months later showed no progression of the thymic tumor and confirmed complete excision of the adrenals. This is a rare case of concomitant CRH and ACTH secretion from a thymic carcinoid tumor; the case illustrates the usefulness of functional imaging with [18F]FDG PET in the diagnosis, management and follow-up of neuroendocrine tumors.

Case report

A 25-year-old woman initially presented with recent-onset depression, hirsuitism, acne and bruising suggestive of Cushing’s syndrome (CS); clinical examination revealed arterial hypertension (170/120 mmHg) and mild proximal myopathy. Subsequent investigations showed hypokalemic alkalosis (serum K+, 2.3 mmol/l (normal range 3.5–5.0 mmol/l); HCO3, 32 mmol/l (normal levels 24±2 mmol/l)), marked hyperandrogenemia (testosterone, 12.5 nmol/l (normal range 0.5–2.5 nmol/l)), normal fasting glucose concentrations and autonomous hypercortisolemia (elevated 24-h urinary free cortisol (UFC) of 4064 nmol per 24 h (normal range 20–300 nmol per 24 h), serum midnight cortisol of 1161 nmol/l and inadequate cortisol suppression to a formal low-dose dexamethasone suppression test).

An ectopic source of adrenocorticotropic hormone (ACTH) secretion was suggested by a marked elevated plasma ACTH concentration (1350 ng/l (normal values <25 ng/l)), and a failure to suppress serum cortisol following a high-dose dexamethasone suppression test (HDDST). Inferior petrosal sinus (IPS) sampling after corticotropin-releasing hormone (CRH) stimulation, however, was more in keeping with Cushing’s disease than with ectopic ACTH production as it showed a brisk ACTH increment following CRH administration (Table 1); a pituitary magnetic resonance imaging (MRI) scan was normal. An initial computed tomography (CT) scan of the thorax was normal but scintigraphy with octreotide 111In-[d-Phe1]-DTPA-octreotide (111In-pentetreotide, Mallinckrodt Medical, St. Louis, MO, USA) showed tracer activity in the thymus (Fig. 1A). A further high-resolution CT showed a 2-cm thymic nodule in the upper mediastinum. Whole-body catheterization and sampling did not reveal an ectopic ACTH source. However, a greater than 3:1 CRH gradient suggestive of ectopic CRH production between the left brachiocephalic vein (BCV) and superior vena cava (SVC) and their simultaneous peripheral samples (BCV, 90 pg/ml and SVC, 100 pg/ml vs 30 pg/ml respectively) was shown. Based on the above findings a working diagnosis of a neuroendpcrine tumor of the thymus (thymic carcinoid tumor) secreting CRH was made.

The patient underwent a mediastinotomy and thymectomy. A central firm nodule within the thymus was totally excised. Histopathology revealed a well-differentiated neuroendocrine carcinoma with tumor invasion into the lymphatic lumina, which stained positively for neuron-specific enolase (NSE), chromogranin A and synaptophysin, ACTH and CRH. The patient made an uneventful recovery and a repeat 111In-pentetreotide scan 2 weeks later showed no tracer uptake in the mediastinum.

Following a prolonged remission the patient presented 8 years later with depression and typical features of CS, suggestive of disease relapse. Further investigations revealed a plasma potassium concentration of 3.6 mmol/l, serum testosterone of 6.8 nmol/l and a 24-h UFC of 32 078 nmol per 24 h. Imaging with 111In-pentetreotide was negative whereas a high-resolution CT scan of the mediastinum showed a possible 2-cm nodule in the thymic bed. Positron emission tomography (PET) using [18F]fluoro-2-deoxy-d-glucose ([18F]FDG) showed increased tracer uptake in the pre-aortic region, implying a metabolically active lesion and prominent uptake of tracer by the adrenals (Fig. 1B and C).

Following a repeated thoracotomy, the histology of the remaining tumor showed relatively monomorphous cells with round nuclei, eosinophilic cytoplasm and prominent nucleoli, mitotic figs. and areas of necrosis. Both vascular and lymphatic invasion was seen. Immunohistochemistry was positive for chromogranin A, synaptophysin, ACTH and cytokeratin but not CRH. Post-operatively, there was little clinical improvement and serum cortisol levels remained elevated. A repeat [18F]FDG PET study showed two small glucose avid areas of uptake adjacent to the thymic bed and persistent avid uptake by the adrenals (standardized uptake values of 5.9 for left and 6.1 for right adrenal). Further thoracic surgery was not thought possible and the patient underwent a successful bilateral adrenalectomy, which lead to clinical and biochemical remission. Plasma ACTH levels remained high. A further [18F]FDG PET study 8 months later showed ongoing activity in the thymic bed but no progression (Fig. 1D); she remains well 2 years after her adrenalectomy.

Discussion

The present case describes an extremely rare case of an ectopic CRH and most probably ACTH co-secreting neuroendocrine tumor manifested as CS; it identifies the usefulness of radionuclear methods in identifying the ectopic source. Although the presenting clinical picture, biochemical findings and negative pituitary imaging were suggestive of ectopic ACTH hypersecretion, this was not substantiated by the results of IPS after CRH stimulation, which were indicative of pituitary ACTH hypersecretion. Subsequent investigation using 111In-labelled octreotide initially revealed the original ectopic source of ACTH secretion while imaging with PET revealed the presence of recurrent disease thus directing to the appropriate treatment. Therefore, the possibility of aberrant hormonal secretion from neuroendocrine tumors should always be considered, particularly when there are confounding biochemical results; in such cases the application of thin-section and spiral CT of the chest should be used as a first line of investigation. If this proves negative, or in cases with small ambiguous lesions where there is a need for confirming their neuroendocrine origin, functional imaging (i.e.111In-labelled octreotide and/or PET) can be extremely helpful in establishing the correct diagnosis (1).

IPS sampling has been claimed to exert an almost 100% sensitivity and specificity in establishing the source of ACTH hypersecretion in cases of ACTH-dependent CS (25). In our case, although the results obtained from the other investigations were consistent with ectopic ACTH CS, IPS revealed a central-to-peripheral ACTH gradient of >3 after CRH stimulation, consistent with Cushing’s disease (2). As these results were originally conflicting we investigated the possibility of the presence of a factor that could de-suppress the pituitary corticotrophs such as CRH, by exerting a stimulating effect. Ectopic CRH secretion, although very rare, has been very well described before and it is a well-established pitfall of IPS when used for the differential diagnosis of ACTH-dependent CS (69). This suspicion was reinforced further when imaging with 111In-labelled octreotide revealed a possible neuroendocrine tumor in the anterior mediastinum, which was confirmed on subsequent CT imaging. Following whole-body catheterization and sampling, a CRH gradient between the left BCV and SVC and their simultaneous peripheral samples (BCV, 90 pg/ml and SVC, 100 pg/ml vs 30 pg/ml respectively) was revealed as indicated from the localization studies. Although sampling from the vena cava did not reveal a gradient for ACTH, we speculate that there was ACTH co-secretion because of the positive immunostaining of the excised tumor.

The difference in peripheral plasma ACTH levels observed at the initial evaluation and during the IPS/peripheral sampling can be explained by the spontaneous fluctuations of CRH secretion by the tumor.

To date, approximately 58 cases of neuroendocrine carcinomas of the thymus associated with CS (mostly attributed to ACTH production) have been reported in the literature (10, 11). Ectopic CRH production, from various tumors, has been documented and these included: a medullary thyroid carcinoma, bronchial carcinoids, a pheochromocytoma, a retropancreatic tumor, a hypothalamic gangliocytoma and small cell carcinoma of the lung and prostate (69, 1215). There have been two reports of thymic CRH production (16, 17). In such cases functional imaging coupled with conventional imaging has recently been used to localize endocrine tumors. In this particular case, prior to repeated thymectomy, [18F]FDG PET scintigraphy and high-resolution CT were the only modalities that detected recurrent tumor. 111In-pentetreotide imaging identified the primary site but failed to localize the site of recurrence, which probably reflects either reduced number or lack of somatostatin receptors in the metastatic lesions. Following the repeated thymectomy, [18F]FDG PET was the only modality that continued to show residual tumor, which was in keeping with the patient’s clinical picture; the high metabolic turnover of the adrenals was also clearly demonstrated. It has been shown that only 5% of normal adrenals are seen on the [18F]FDG PET scan. When co-registered [18F]FDG PET/CT studies are quantified the adrenal uptake is fairly low with standardized uptake values ranging between 0.95 and 2.46 (18).

PET using [18F]FDG reflects the glucose turnover in a lesion. Increased tracer uptake implies increased metabolic activity of a lesion. This imaging technique plays an important role in identifying cancer stages and the investigation of tumor recurrence (19, 20). [18F]FDG PET imaging has a high sensitivity, specificity and accuracy (70–95%) depending on the type of tumor being investigated (19). However, application of this imaging modality in neuroendocrine tumors is limited because they are mostly well differentiated with a low metabolic rate and therefore cannot be efficiently visualized with FDG (21, 22). PET imaging using [11C]5-hydroxytryptophan ([11C]5-HTP) or [11C]l-DOPA has been shown to be more sensitive for visualization of carcinoids and other neuroendocrine tumors (20, 2325). Recent technological development in hardware allows simultaneous data acquisition of [18F]FDG PET and CT in one sweep. Thus fusion of the two images allows accurate localization of small functional and non-functional lesions. In our case, this well-differentiated CRH/ACTH secreting tumor was well visualized with [18F]FDG due to increased metabolic activity. There have been two other case reports where [18F]FDG PET has been used to localize a thymic carcinoid tumor (26) and an ectopic ACTH-secreting bronchial carcinoid tumor (27).

In summary, this is a rare case of CRH and probable ACTH co-secretion of a well-differentiated neuroendocrine carcinoma, where in addition to conventional imaging functional scintigraphic imaging with 111In-pentetreotide and [18F]FDG PET was used for tumor localization and follow-up.

Table 1

Inferior petrosal sinus (IPS) sampling with CRH stimulation.

ACTH (ng/l)
Time (min)Left IPSRight IPSPeripheral
04791110364
315001960434
89901900490
155261760498
Figure 1
Figure 1

Patient with thymic carcinoid tumor. (A) 111In-pentetreotide scan shows tracer uptake in the thymus (curved arrow). (B and C) [18F]FDG PET images: coronal sections show [18F]FDG avid thymic lesion (large arrow) and a further coronal section more posteriorly shows high uptake in the adrenal glands (small arrows). (D) [18F]FDG PET study acquired post-thymectomy and post-adrenalectomy shows activity in residual tissue (large arrow).

Citation: European Journal of Endocrinology eur j endocrinol 152, 4; 10.1530/eje.1.01839

References

  • 1

    Tabarin A, Valli N, Chanson P, Bachelot Y, Rohmer V, Bex-Bachellerie V, Gatargi B, Roger P & Laurent F. Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic adrenocorticotropin syndrome. Journal of Clinical Endocrinology and Metabolism 1999 84 1193–1202.

    • Search Google Scholar
    • Export Citation
  • 2

    Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler GB Jr & Loriaux DL. Petrosal sinus sampling with and without corticotrophin-releasing hormone for the differential diagnosis of Cushing’s syndrome. New England Journal of Medicine 1991 325 897–905.

    • Search Google Scholar
    • Export Citation
  • 3

    Landolt AM, Schubiger O, Maurer R & Girard J. The value of inferior petrosal sinus sampling in diagnosis and treatment of Cushing’s disease. Clinical Endocrinology 1994 40 485–492.

    • Search Google Scholar
    • Export Citation
  • 4

    Kaltsas GA, Giannulis MG, Newell-Price JD, Dacie JE, Thakkar C, Afshar F, Monson JP, Grossman AB, Besser GM & Trainer PJ. A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing’s disease and the occult ectopic adrenocorticotropin syndrome. Journal of Clinical Endocrinology and Metabolism 1999 84 487–492.

    • Search Google Scholar
    • Export Citation
  • 5

    Newell-Price J & Grossman AB. The differential diagnosis of Cushing’s syndrome. Annals of Endocrinology 2001 62 173–179.

  • 6

    Case records of the Massachusetts General Hospital. A 20-year-old woman with Cushing’s disease and a pulmonary module. New England Journal of Medicine 1987 317 1648–1658.

    • Search Google Scholar
    • Export Citation
  • 7

    O’Brien T, Young WF Jr, Davila DG, Scheithauer BW, Kovacs K, Horvath E, Vale W & Van Heerden JA. Cushing’s syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a pheochromocytoma. Clinical Endocrinology 1992 37 460–467.

    • Search Google Scholar
    • Export Citation
  • 8

    Young J, Deneux C, Grino M, Oliver C, Chanson P & Schaison G. Pitfall of petrosal sinus sampling in a Cushing’s syndrome secondary to ectopic adrenocorticotropin-corticotropin releasing hormone (ACTH-CRH) secretion. Journal of Clinical Endocrinology and Metabolism 1998 83 305–308.

    • Search Google Scholar
    • Export Citation
  • 9

    Lefournier V, Martinie M, Vasdev A, Bessou P, Passagia JG, Labat-Moleur F, Sturm N, Bosson JL, Bachelot I & Chabre O. Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing’s disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage. Journal of Clinical Endocrinology and Metabolism 2003 88 196–203.

    • Search Google Scholar
    • Export Citation
  • 10

    Soga J, Yakuwa Y & Osaka M. Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties. Review. Annals of Thoracic Cardiovascular Surgery 1999 5 285–291.

    • Search Google Scholar
    • Export Citation
  • 11

    Perrot de M, Spiliopoulos A, Fischer S, Totsch M & Keshavjee S. Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing’s syndrome. Annals of Thoracic Surgery 2002 73 675–681.

    • Search Google Scholar
    • Export Citation
  • 12

    Eriksson B, Arnberg H, Oberg K, Hellman U, Lundqvist G, Wernstedt C & Wilander E. A polyclonal antiserum against chromogranin A and B: a new sensitive marker for neuroendocrine tumors. Acta Endocrinologica 1990 122 145–155.

    • Search Google Scholar
    • Export Citation
  • 13

    Grander D, Oberg K, Lundqvist ML, Janson ET, Eriksson B & Einhorn S. Interferon-induced enhancement of 2,5 oligoadenylate synthetase in mid-gut carcinoid tumors. Lancet 1990 336 337–340.

    • Search Google Scholar
    • Export Citation
  • 14

    Krenning EP, Kooij PP, Bakker WH, Breeman WA, Postema PT, Kwekkeboom DJ, Oei HY, DeJong M, Visser TS & Reijs AE. Radiotherapy with a radiolabaled somatostatin analogue: a case history. Annals of the New York Academy of Sciences 1994 733 496–506.

    • Search Google Scholar
    • Export Citation
  • 15

    Moertel CG, Johnson CM, McKusick MA, Martin JK Jr, Nagorney DM, Kvols LK, Rubin J & Kunselman S. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Annals of Internal Medicine 1994 120 302–309.

    • Search Google Scholar
    • Export Citation
  • 16

    Ozawa Y, Tomoyasu H, Takeshita A, Shishiba Y, Yamada S, Kovacs K & Matsushita H. Shift from CRH to ACTH production in a thymic carcinoid with Cushing’s syndrome. Hormone Research 1996 45 264–268.

    • Search Google Scholar
    • Export Citation
  • 17

    Shikawa T, Inone C, Sasaki H, Saton K & Kimura N. Thymic carcinoid associated with ectopic ACTH syndrome. In Japanese. Nihoh Kyobu Shikkan Gakkai Zasshi 1996 34 471–476.

    • Search Google Scholar
    • Export Citation
  • 18

    Bagheri B, Maurer AH, Doss M & Adler L. Characterisation of the normal adrenal gland with 18F-FDGPET/CT. Journal of Nuclear Medicine 2004 45 1340–1343.

    • Search Google Scholar
    • Export Citation
  • 19

    Bomanji JB, Costa DC & Ell PJ. Clinical role of positron emission tomography in oncology. Lancet Oncology 2001 3 157–164.

  • 20

    Eriksson B, Bergstrom M, Sundin A, Juhlin C, Orlefors H, Oberg K & Langstrom B. The role of PET in localization of neuroendocrine and adrenocortical tumors. Annals of the New York Academy of Sciences 2002 970 159–169.

    • Search Google Scholar
    • Export Citation
  • 21

    Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH & Hor G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumors. European Journal of Nuclear Medicine 2001 25 79–83.

    • Search Google Scholar
    • Export Citation
  • 22

    Erasmus JJ, McAdams HP, Patz EF, Coleman RE, Ahuja V & Goodman PC. Evaluation of primary pulmonary carcinoid tumors using FDG PET. American Journal of Roentgenology 1998 170 1369–1373.

    • Search Google Scholar
    • Export Citation
  • 23

    Orlefors H, Sundin A, Ahlstrom H, Bjurling P, Bergstrom M, Lilja A, Langstrom B, Oberg K & Eriksson B. Positron emission tomography with 5-hydroxytryptophan in neuroendocrine tumors. Journal of Clinical Oncology 1998 16 2534–2541.

    • Search Google Scholar
    • Export Citation
  • 24

    Mignon M. Natural history of neuroendocrine enteropancreatic tumors. Digestion 2000 62 51–58.

  • 25

    Sundin A, Eriksson B, Bergstrom M, Langsrom B, Oberg K & Orlefors H. PET in the diagnosis of neuroendocrine tumors. Annals of the New York Academy of Sciences 2004 1014 246–257.

    • Search Google Scholar
    • Export Citation
  • 26

    Groves AM, Mohan HK, Wegner EA, Ham SF, Bingham SB & Clarke SE. PET with FDG to show thymic carcinoid. American Journal of Roentgenology 2004 82 511–513.

    • Search Google Scholar
    • Export Citation
  • 27

    Biering H, Pirlich M, Bauditz J, Sandrock D, Lochs H & Gerl H. PET scan in occult ectopic ACTH syndrome: a useful tool? Clinical Endocrinology 2003 59 404–405.

    • Search Google Scholar
    • Export Citation

 

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    Patient with thymic carcinoid tumor. (A) 111In-pentetreotide scan shows tracer uptake in the thymus (curved arrow). (B and C) [18F]FDG PET images: coronal sections show [18F]FDG avid thymic lesion (large arrow) and a further coronal section more posteriorly shows high uptake in the adrenal glands (small arrows). (D) [18F]FDG PET study acquired post-thymectomy and post-adrenalectomy shows activity in residual tissue (large arrow).

  • 1

    Tabarin A, Valli N, Chanson P, Bachelot Y, Rohmer V, Bex-Bachellerie V, Gatargi B, Roger P & Laurent F. Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic adrenocorticotropin syndrome. Journal of Clinical Endocrinology and Metabolism 1999 84 1193–1202.

    • Search Google Scholar
    • Export Citation
  • 2

    Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler GB Jr & Loriaux DL. Petrosal sinus sampling with and without corticotrophin-releasing hormone for the differential diagnosis of Cushing’s syndrome. New England Journal of Medicine 1991 325 897–905.

    • Search Google Scholar
    • Export Citation
  • 3

    Landolt AM, Schubiger O, Maurer R & Girard J. The value of inferior petrosal sinus sampling in diagnosis and treatment of Cushing’s disease. Clinical Endocrinology 1994 40 485–492.

    • Search Google Scholar
    • Export Citation
  • 4

    Kaltsas GA, Giannulis MG, Newell-Price JD, Dacie JE, Thakkar C, Afshar F, Monson JP, Grossman AB, Besser GM & Trainer PJ. A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing’s disease and the occult ectopic adrenocorticotropin syndrome. Journal of Clinical Endocrinology and Metabolism 1999 84 487–492.

    • Search Google Scholar
    • Export Citation
  • 5

    Newell-Price J & Grossman AB. The differential diagnosis of Cushing’s syndrome. Annals of Endocrinology 2001 62 173–179.

  • 6

    Case records of the Massachusetts General Hospital. A 20-year-old woman with Cushing’s disease and a pulmonary module. New England Journal of Medicine 1987 317 1648–1658.

    • Search Google Scholar
    • Export Citation
  • 7

    O’Brien T, Young WF Jr, Davila DG, Scheithauer BW, Kovacs K, Horvath E, Vale W & Van Heerden JA. Cushing’s syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a pheochromocytoma. Clinical Endocrinology 1992 37 460–467.

    • Search Google Scholar
    • Export Citation
  • 8

    Young J, Deneux C, Grino M, Oliver C, Chanson P & Schaison G. Pitfall of petrosal sinus sampling in a Cushing’s syndrome secondary to ectopic adrenocorticotropin-corticotropin releasing hormone (ACTH-CRH) secretion. Journal of Clinical Endocrinology and Metabolism 1998 83 305–308.

    • Search Google Scholar
    • Export Citation
  • 9

    Lefournier V, Martinie M, Vasdev A, Bessou P, Passagia JG, Labat-Moleur F, Sturm N, Bosson JL, Bachelot I & Chabre O. Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing’s disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage. Journal of Clinical Endocrinology and Metabolism 2003 88 196–203.

    • Search Google Scholar
    • Export Citation
  • 10

    Soga J, Yakuwa Y & Osaka M. Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties. Review. Annals of Thoracic Cardiovascular Surgery 1999 5 285–291.

    • Search Google Scholar
    • Export Citation
  • 11

    Perrot de M, Spiliopoulos A, Fischer S, Totsch M & Keshavjee S. Neuroendocrine carcinoma (carcinoid) of the thymus associated with Cushing’s syndrome. Annals of Thoracic Surgery 2002 73 675–681.

    • Search Google Scholar
    • Export Citation
  • 12

    Eriksson B, Arnberg H, Oberg K, Hellman U, Lundqvist G, Wernstedt C & Wilander E. A polyclonal antiserum against chromogranin A and B: a new sensitive marker for neuroendocrine tumors. Acta Endocrinologica 1990 122 145–155.

    • Search Google Scholar
    • Export Citation
  • 13

    Grander D, Oberg K, Lundqvist ML, Janson ET, Eriksson B & Einhorn S. Interferon-induced enhancement of 2,5 oligoadenylate synthetase in mid-gut carcinoid tumors. Lancet 1990 336 337–340.

    • Search Google Scholar
    • Export Citation
  • 14

    Krenning EP, Kooij PP, Bakker WH, Breeman WA, Postema PT, Kwekkeboom DJ, Oei HY, DeJong M, Visser TS & Reijs AE. Radiotherapy with a radiolabaled somatostatin analogue: a case history. Annals of the New York Academy of Sciences 1994 733 496–506.

    • Search Google Scholar
    • Export Citation
  • 15

    Moertel CG, Johnson CM, McKusick MA, Martin JK Jr, Nagorney DM, Kvols LK, Rubin J & Kunselman S. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Annals of Internal Medicine 1994 120 302–309.

    • Search Google Scholar
    • Export Citation
  • 16

    Ozawa Y, Tomoyasu H, Takeshita A, Shishiba Y, Yamada S, Kovacs K & Matsushita H. Shift from CRH to ACTH production in a thymic carcinoid with Cushing’s syndrome. Hormone Research 1996 45 264–268.

    • Search Google Scholar
    • Export Citation
  • 17

    Shikawa T, Inone C, Sasaki H, Saton K & Kimura N. Thymic carcinoid associated with ectopic ACTH syndrome. In Japanese. Nihoh Kyobu Shikkan Gakkai Zasshi 1996 34 471–476.

    • Search Google Scholar
    • Export Citation
  • 18

    Bagheri B, Maurer AH, Doss M & Adler L. Characterisation of the normal adrenal gland with 18F-FDGPET/CT. Journal of Nuclear Medicine 2004 45 1340–1343.

    • Search Google Scholar
    • Export Citation
  • 19

    Bomanji JB, Costa DC & Ell PJ. Clinical role of positron emission tomography in oncology. Lancet Oncology 2001 3 157–164.

  • 20

    Eriksson B, Bergstrom M, Sundin A, Juhlin C, Orlefors H, Oberg K & Langstrom B. The role of PET in localization of neuroendocrine and adrenocortical tumors. Annals of the New York Academy of Sciences 2002 970 159–169.

    • Search Google Scholar
    • Export Citation
  • 21

    Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH & Hor G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumors. European Journal of Nuclear Medicine 2001 25 79–83.

    • Search Google Scholar
    • Export Citation
  • 22

    Erasmus JJ, McAdams HP, Patz EF, Coleman RE, Ahuja V & Goodman PC. Evaluation of primary pulmonary carcinoid tumors using FDG PET. American Journal of Roentgenology 1998 170 1369–1373.

    • Search Google Scholar
    • Export Citation
  • 23

    Orlefors H, Sundin A, Ahlstrom H, Bjurling P, Bergstrom M, Lilja A, Langstrom B, Oberg K & Eriksson B. Positron emission tomography with 5-hydroxytryptophan in neuroendocrine tumors. Journal of Clinical Oncology 1998 16 2534–2541.

    • Search Google Scholar
    • Export Citation
  • 24

    Mignon M. Natural history of neuroendocrine enteropancreatic tumors. Digestion 2000 62 51–58.

  • 25

    Sundin A, Eriksson B, Bergstrom M, Langsrom B, Oberg K & Orlefors H. PET in the diagnosis of neuroendocrine tumors. Annals of the New York Academy of Sciences 2004 1014 246–257.

    • Search Google Scholar
    • Export Citation
  • 26

    Groves AM, Mohan HK, Wegner EA, Ham SF, Bingham SB & Clarke SE. PET with FDG to show thymic carcinoid. American Journal of Roentgenology 2004 82 511–513.

    • Search Google Scholar
    • Export Citation
  • 27

    Biering H, Pirlich M, Bauditz J, Sandrock D, Lochs H & Gerl H. PET scan in occult ectopic ACTH syndrome: a useful tool? Clinical Endocrinology 2003 59 404–405.

    • Search Google Scholar
    • Export Citation